EP0264989A1 - Formes galéniques par voie orale à libération prolongée de dérivés de rhein - Google Patents

Formes galéniques par voie orale à libération prolongée de dérivés de rhein Download PDF

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Publication number
EP0264989A1
EP0264989A1 EP87201845A EP87201845A EP0264989A1 EP 0264989 A1 EP0264989 A1 EP 0264989A1 EP 87201845 A EP87201845 A EP 87201845A EP 87201845 A EP87201845 A EP 87201845A EP 0264989 A1 EP0264989 A1 EP 0264989A1
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
release
composition according
delayed release
rhein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP87201845A
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German (de)
English (en)
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EP0264989B1 (fr
Inventor
Vanna Springolo
Germano Coppi
Mario Ercole Scevola
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Proter SpA
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • rhein of particularly of diacetylrhein are drugs endowed with a relevant antiarthrosic, analgesic and anti-inflammatory activity (Italian Patent No. 1098332).
  • the present invention relates to a number of formulations for oral use with slow release of dyacetylrhein and other derivatives of rhein for therapeutical purposes.
  • the present invention relate to the preparation of rhein derivatives and particularly of dyacetylrhein derivatives in pharmaceutical formulations which permit a gradual and programmed release of the drug and such as to ensure a pharmacologically active hematic level throughout the period of 24 hours from the administration of the therapeutical dose of the drug.
  • Some examples of formulation of rhein derivatives with slow release of the drug are hereinafter described, which have been controlled by the in vitro release test as well as by determining the hematic levels of the drug after experimental administration to animals.
  • 500 g of dyacetylrhein with granule size of between 50 and 100 ⁇ m are carefully admixed with 150 g of finely powdered saccharose and 150 g of Magnolia starch; the mixture is finely ground and then supported onto 1000 g of micronuclei having about 0.4 mm of diameter by wetting with a solution containing 37.5 of polyvinylpyrrolidone.
  • the granulate is dried in an hot air oven, the dried granulate is sieved to prepare end granules of uniform size which are, in portions, coated in a basin with a 20% polyvinil pyrrolidone and 30% shellac solution isopropanol.
  • the number of applications of the coating solution onto the several portion of the granules is adjusted as a function of the release times as experimentally measured by means of the in vitro test.
  • the granules with different coating degrees are admixed as a function of the related release times measured so as to obtain in the same posologic unit (for example a capsule of hard gelatin) the desired amount of drug (for example 100 mg) and the release of the active principle within the programmed times (for instance 24 hours).
  • the desired amount of drug for example 100 mg
  • the desired amount of drug for example 100 mg
  • the release of the active principle within the programmed times (for instance 24 hours).
  • dipropionylrhein 150g are uniformly admixed with 300 g of lactose, 5 g of dispersed slicon dioxide ,15 g of magnesium stearate, 20 g of talc. Separately 350 g of dipropionylrhein are carefully admixed with 350 g of titanium dioxide, 115 g of polyvinylpy rrolidone and 25 g of triacetin. This mixture is wetted until a granulate is obtained which is dried in an hot air oven, The granules are coated in portions into a basin with an acetone solution of cellulose acetophtalate by adjusting the number of applications as a function of the release time to be obtained.
  • the mixture of the powders and the granulates with different coating degree are in turn admixed as a function of the related release times as determined in the in vitro test so as to obtain in the same posologic unit (for instance gelatin capsules, tablets, granulates, etc.) the desired amount of drug and the release of the active principle within the programmed time.
  • posologic unit for instance gelatin capsules, tablets, granulates, etc.
  • diacetylrhein 500 g of diacetylrhein are carefully admixed with 10 g of polyvinylpyrrolidone, 50 g of microcrystalline cellulose , 100 g of sodium citrate; the mixture is wet granulated with water and the granulate is dried in a hot air oven.
  • soya polisaccharides 10 g of talc and 150 g of magnesium stearate are admixed and the mixture is wet granulated and dried.
  • the two combined granulates are converted into tablets by means of a pressing machine and resulting tablets are coated by subsequent application of ethanol solution containing 40g of hydroxypropyl-methylcellulose, phtalate, 10 g of acetylated monoglyceride and 10 g of titanium dioxide.
  • the capsules obtained according to examples 1 and 3 are tested by means of an in vitro release test according to the method reported in U.S.P. XXI.
  • the diacetylrhein has been administered in the two pharmaceutical forms according to a "cross-over" experimental scheme at the dose of 20 ml/kg and with a washout time of a week.
  • the blood sampling has been carried out at the time 0 (basal) and after 1, 2, 4, 8, 12, 16, 20 and 20 hours after the treatment.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Rheumatology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP87201845A 1986-10-01 1987-09-25 Formes galéniques par voie orale à libération prolongée de dérivés de rhein Expired - Lifetime EP0264989B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT21867/86A IT1197316B (it) 1986-10-01 1986-10-01 Formulazione galenica ad uso orale di derivati della reina a lento rilascio per impiego terapeutico
IT2186786 1986-10-01

Publications (2)

Publication Number Publication Date
EP0264989A1 true EP0264989A1 (fr) 1988-04-27
EP0264989B1 EP0264989B1 (fr) 1991-12-18

Family

ID=11187979

Family Applications (1)

Application Number Title Priority Date Filing Date
EP87201845A Expired - Lifetime EP0264989B1 (fr) 1986-10-01 1987-09-25 Formes galéniques par voie orale à libération prolongée de dérivés de rhein

Country Status (5)

Country Link
US (1) US4861599A (fr)
EP (1) EP0264989B1 (fr)
JP (1) JP2572781B2 (fr)
DE (1) DE3775335D1 (fr)
IT (1) IT1197316B (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993017673A1 (fr) * 1992-03-03 1993-09-16 Top Gold Pty., Limited Analgesique a liberation controlee
EP0809995A1 (fr) * 1996-04-29 1997-12-03 Trans Bussan S.A. Nouvelles formulations de la diacerhéine obtenues par inclusion du principe actif dans des hydrogels polysaccharidiques
NL1003503C2 (nl) * 1996-07-04 1998-01-07 Negma Steba International Dev Farmaceutische samenstelling voor orale toediening.
WO2001012164A1 (fr) * 1999-08-12 2001-02-22 Merck Patent Gmbh Forme de presentation orale contenant des micro-organismes probiotiques
WO2001051044A2 (fr) * 2000-01-12 2001-07-19 Laboratoire Medidom S.A. Substances utilisees dans le traitement du psoriasis
EP2280697A1 (fr) * 2008-04-30 2011-02-09 Wockhardt Research Centre Compositions liquides orales de rhéine ou de diacéréine
EP2520284A1 (fr) 2007-09-27 2012-11-07 Wockhardt Limited Compositions pharmaceutiques de rhéine ou de diacéréine

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5395626A (en) * 1994-03-23 1995-03-07 Ortho Pharmaceutical Corporation Multilayered controlled release pharmaceutical dosage form
US8101209B2 (en) 2001-10-09 2012-01-24 Flamel Technologies Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles
US8821924B2 (en) 2007-09-14 2014-09-02 Wockhardt Ltd. Rhein or diacerein compositions
US20100285114A1 (en) * 2007-09-27 2010-11-11 Rahul Dabre Pharmaceutical compositions of rhein or diacerein
TWI473610B (zh) * 2008-10-28 2015-02-21 Twi Biotechnology Inc 包含雙醋瑞因（ｄｉａｃｅｒｅｉｎ）之醫藥組合物
KR101751906B1 (ko) 2009-03-04 2017-06-29 엠플리큐어 아베 새로운 오용 방지 배합물
MX2011011829A (es) 2009-05-08 2012-02-21 Orexo Ab Composicion para suministro sostenido de farmaco que comprende un aglutinante geopolimerico.
ES2658913T3 (es) 2010-09-07 2018-03-12 Emplicure Ab Dispositivo de administración transdérmica de un fármaco
CA2936748C (fr) 2014-10-31 2017-08-08 Purdue Pharma Methodes et compositions destinees au traitement du trouble de deficit d'attention
US10722473B2 (en) 2018-11-19 2020-07-28 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0149920A2 (fr) * 1983-12-22 1985-07-31 ELAN CORPORATION, Plc Formulation pharmaceutique

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2336218C3 (de) * 1973-07-17 1985-11-14 Byk Gulden Lomberg Chemische Fabrik Gmbh, 7750 Konstanz Orale Arzneiform
DK151608C (da) * 1982-08-13 1988-06-20 Benzon As Alfred Fremgangsmaade til fremstilling af et farmaceutisk peroralt polydepotpraeparat med kontrolleret afgivelse
CH658188A5 (de) * 1984-03-23 1986-10-31 Ciba Geigy Ag Lagerstabile schnellzerfallende pharmazeutische presslinge.
IT1200217B (it) * 1986-09-30 1989-01-05 Valducci Roberto Membrana per uso farmaceutico ed industriale

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0149920A2 (fr) * 1983-12-22 1985-07-31 ELAN CORPORATION, Plc Formulation pharmaceutique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 100, no. 18, 30th April 1984, page 365, abstract no. 144991e, Columbus, Ohio, US; & JP-A-58 225 015 (PROTER S.p.A.) 27-12-1983 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993017673A1 (fr) * 1992-03-03 1993-09-16 Top Gold Pty., Limited Analgesique a liberation controlee
EP0809995A1 (fr) * 1996-04-29 1997-12-03 Trans Bussan S.A. Nouvelles formulations de la diacerhéine obtenues par inclusion du principe actif dans des hydrogels polysaccharidiques
NL1003503C2 (nl) * 1996-07-04 1998-01-07 Negma Steba International Dev Farmaceutische samenstelling voor orale toediening.
WO1998001118A1 (fr) * 1996-07-04 1998-01-15 Negma-Steba International Development N.V. Composition pharmaceutique pour administration par voie orale
US5952383A (en) * 1996-07-04 1999-09-14 Negma-Steba International Development N.V. Pharmaceutical composition for oral delivery
WO2001012164A1 (fr) * 1999-08-12 2001-02-22 Merck Patent Gmbh Forme de presentation orale contenant des micro-organismes probiotiques
WO2001051044A2 (fr) * 2000-01-12 2001-07-19 Laboratoire Medidom S.A. Substances utilisees dans le traitement du psoriasis
WO2001051044A3 (fr) * 2000-01-12 2002-03-28 Medidom Lab Substances utilisees dans le traitement du psoriasis
CZ301129B6 (cs) * 2000-01-12 2009-11-11 Laboratoire Medidom S. A. Farmaceutický prípravek obsahující diacerein pro lécení psoriázy a s ní sdružených onemocnení
EP2520284A1 (fr) 2007-09-27 2012-11-07 Wockhardt Limited Compositions pharmaceutiques de rhéine ou de diacéréine
EP2520283A1 (fr) 2007-09-27 2012-11-07 Wockhardt Limited Compositions pharmaceutiques de rhéine ou de diacéréine
EP2520285A1 (fr) 2007-09-27 2012-11-07 Wockhardt Limited Compositions pharmaceutiques de rhéine ou de diacéréine
EP2520286A1 (fr) 2007-09-27 2012-11-07 Wockhardt Limited Compositions pharmaceutiques de rhéine ou de diacéréine
EP2280697A1 (fr) * 2008-04-30 2011-02-09 Wockhardt Research Centre Compositions liquides orales de rhéine ou de diacéréine

Also Published As

Publication number Publication date
US4861599A (en) 1989-08-29
IT8621867A0 (it) 1986-10-01
JP2572781B2 (ja) 1997-01-16
JPS63146816A (ja) 1988-06-18
DE3775335D1 (de) 1992-01-30
EP0264989B1 (fr) 1991-12-18
IT8621867A1 (it) 1988-04-01
IT1197316B (it) 1988-11-30

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